Development of a plant-derived virus-like particle vaccine against SARS-CoV

开发针对 SARS-CoV 的植物源病毒样颗粒疫苗

• 批准号: 7472041
• 负责人: Zhong Huang
• 金额: $ 18.77万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472041
• 关键词: Adjuvant; Antibodies; Antibody Formation; Antigens; Biochemical; Biological Assay; CD8B1 gene; Capsid Proteins; Categories; Cells; Cessation of life; Clinical; Coronavirus; Coronavirus spike protein; Development; Disease; Disease Outbreaks; Drug Formulations; Elderly; Electron Microscopy; Enhancing Antibodies; Epitopes; Future; Goals; Hepatitis B; Hepatitis B Core Antigen; Hepatitis B Surface Antigens; Human Papillomavirus; IgG1; Immune response; Immunity; Immunization; Immunodominant Epitopes; Immunoglobulin G; Individual; Infection; Knowledge; L1 viral capsid protein; Laboratories; Life; Lung; Molecular Biology; Mucosal Immunity; Mus; Norwalk virus capsid; Numbers; Organ; Peptidyl-Dipeptidase A; Phase; Phase I Clinical Trials; Plant Leaves; Plant Viruses; Plants; Production; Property; Protein Binding; Proteins; Public Health; Rate; Recombinants; Replicon; Research; SARS coronavirus; Secretory Immunoglobulin A; Serum; Severe Acute Respiratory Syndrome; Staining method; Stains; Standards of Weights and Measures; Subunit Vaccines; Sucrose; Surface; System; T-Lymphocyte; Testing; Vaccination; Vaccines; Virus; Virus Replication; Virus-like particle; aluminum sulfate; base; biodefense; cytokine; dosage; enzyme linked immunospot assay; immunogenic; immunogenicity; mortality; mouse model; mucosal vaccine; neutralizing antibody; novel; pathogen; receptor; receptor binding; research study; response; vaccine development

DESCRIPTION (provided by applicant): Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus. During the outbreak in 2002/2003 the disease spread internationally resulting in an overall mortality rate of ~10% and a significantly higher rate of ~40% for elderly individuals. As is the case with other coronaviruses, the spike (S) protein is the major target for neutralizing antibodies. SARS-CoV S protein binds to the receptor, angiotensin-converting enzyme 2 (ACE2), through its receptor binding domain (RBD). The RBD is immunogenic and is a major neutralizing determinant. Significant research has been directed toward vaccine development, but none is yet available. Concerns remain over the possibility of future outbreaks of SARS. The reservoir for the virus has not been identified. SARS-CoV is a Biodefense Category C priority pathogen. There is also the potential for laboratory acquired infections. Thus, development of effective vaccines is still of significant importance. The long-term goal of this project is to determine if plant-derived virus-like particles presenting the RBD of the SARS-CoV S protein can efficiently stimulate protective systemic and mucosal immunity against SARS-CoV. Novel heterologous VLPs displaying the RBD will be generated by expressing the RBD as fusions with the hepatitis B surface (HBsAg) and core (HBcAg) antigens in plants. RBD-containing VLPs will be evaluated for their ability to elicit strong systemic and mucosal SARS-CoV-neutralizing antibody responses and protective immunity in mice. Standard molecular biology, biochemical approaches, vaccination and immunological assays will be used. The specific aims of the project are: 1. To produce heterologous VLPs presenting the SARS-CoV S RBD in plants; and 2. To evaluate the immunogenicity and protective efficacy of plant-derived VLPs in mouse models. PUBLIC HEALTH RELEVANCE: Severe acute respiratory syndrome (SARS) caused by a new coronavirus (SARS-CoV) is new disease that appeared in 2002/2003 which caused a significant number of infections and deaths worldwide, with a mortality rate of at least 40% in older individuals. Even though the global outbreak was contained, there are concerns that the virus will reemerge or that it could potentially be used as a bioterrorist agent, thus it is important to develop safe effective vaccines. The long term goal of this project is to develop a novel subunit vaccine that elicits protection against SARS coronavirus.

描述（由申请人提供）：严重急性呼吸系统综合症（SARS）是由一种新出现的冠状病毒引起的。 2002/2003 年疫情爆发期间，该疾病在国际范围内传播，导致总体死亡率约为 10%，老年人的死亡率明显更高，约为 40%。与其他冠状病毒一样，刺突 (S) 蛋白是中和抗体的主要目标。 SARS-CoV S 蛋白通过其受体结合域 (RBD) 与受体血管紧张素转换酶 2 (ACE2) 结合。 RBD 具有免疫原性，是主要的中和决定因素。已经针对疫苗开发进行了大量研究，但目前还没有任何可用的研究。人们仍然担心未来可能爆发非典。该病毒的储存库尚未确定。 SARS-CoV 是生物防御 C 类优先病原体。还存在实验室获得性感染的可能性。因此，开发有效的疫苗仍然具有重要意义。该项目的长期目标是确定呈现 SARS-CoV S 蛋白 RBD 的植物源性病毒样颗粒是否可以有效刺激针对 SARS-CoV 的保护性系统和粘膜免疫。展示RBD的新型异源VLP将通过在植物中将RBD表达为与乙型肝炎表面(HBsAg)和核心(HBcAg)抗原的融合物来产生。将评估含有 RBD 的 VLP 在小鼠体内引发强烈的全身和粘膜 SARS-CoV 中和抗体反应和保护性免疫的能力。将使用标准分子生物学、生化方法、疫苗接种和免疫学测定。该项目的具体目标是： 1. 生产在植物中呈递 SARS-CoV S RBD 的异源 VLP； 2. 评估植物源性病毒样颗粒在小鼠模型中的免疫原性和保护功效。 公共卫生相关性：由新型冠状病毒 (SARS-CoV) 引起的严重急性呼吸综合征 (SARS) 是 2002/2003 年出现的新疾病，在全世界造成大量感染和死亡，老年人死亡率至少为 40%。尽管全球疫情得到遏制，但人们担心该病毒会再次出现或可能被用作生物恐怖分子，因此开发安全有效的疫苗非常重要。该项目的长期目标是开发一种新型亚单位疫苗，可针对 SARS 冠状病毒提供保护。